Training Grant in Cancer Pharmacology. The purpose of the multidisciplinary Cancer Pharmacology training program is to provide predoctoral and postdoctoral students with a training environment that does not currently exist at the University of Pennsylvania. Drs. Blair (Program Director), Penning (Program Co-Director) and Assoian (Program Co-Director) have provided the sustained leadership required to develop a multidisciplinary program in molecular mechanisms of multi-stage carcinogenesis. There is now a real need for similar sustained leadership to be applied to the recruitment and training of both predoctoral and postdoctoral scientists in the multidisciplinary environment required for the field of cancer pharmacology. Major advances in the treatment of cancer patients in the next decade will result from multidisciplinary approaches in understanding of how malignant cells work at the molecular level and in designing novel therapeutic agents to disrupt these processes. Therefore, the proposed training program will help fill the current deficit of individuals qualified to develop the next generation of chemotherapeutic agents. The ultimate goal of the program is to provide training in cancer pharmacology that goes from laboratory to bedside and back again. Specifically, trainees will learn how cancer pharmacology can be used to identify new targets, how small molecules are synthesized and tested against these targets, how they are used in Phase I trials, how Phase I studies are developed into full clinical trials, and how epidemiology and pharmacogenetics are utilized to assess efficacy and lead to the discovery of new targets. Trainees will also receive specific training in how to project quantitative measures of drug effect from proof of concept in model systems into the rational selection of dosing in humans. These goals will be accomplished through the courses that are offered and the multidisciplinary research experiences that will be available from the faculty. The 26 faculty mentors with diverse complementary expertise are grouped into three programs: A. Pharmacology Discovery and Development. B. Cell and Molecular Cancer Pharmacology. C. Clinical Cancer Pharmacology. The trainees will have research mentors from two of these programs. The mentors on this proposed program have a very strong record of accomplishment as cancer researchers. They are Principal Investigators or Project Leaders on 68 NIH grants of which 39 (57%) are from NCI (27 RO-1s, 8 PO-1 Projects, 1 PO-1 Scientific Core, 1 P30 Scientific Core, 1 UO-1, 1 T-32). Apart from training grants, 11 of the mentors have NIH-funded (primarily through NCI) collaborative research grants. The mentors serve on Editorial Boards of 23 Journals and two of them are Journal Editors. Over the past 10-years, the mentors have trained 105 predoctoral students and 250 postdoctoral fellows; they currently have 52 predoctoral and 76 postdoctoral trainees in their laboratories. The mentors have clearly demonstrated that they have the scientific expertise and training experience to develop a new multidisciplinary training program in Cancer Pharmacology. Mentors have superb access to different patient populations through their association with 11 NCI-funded clinical programs. Furthermore, one of the mentors is Director of the General Clinical Research Center at the University of Pennsylvania (Dr. FitzGerald) and one is acting Director of the General Clinical Research Center at Children's Hospital of Philadelphia (Dr. Adamson). Both of these mentors have research programs with a focus on translational therapeutics and so they provide another outstanding training resource.